The ability to detect and identify explosives, drugs, and chemical and biological agents, as well as the ability to monitor air and water quality, has become increasingly more important given increasing terrorist and military activities and environmental concerns. Spectrometry is a powerful analytical tool for identifying molecular components of these substances. Certain known methods for detection and/or quantification of the concentration of such components include conventional mass spectrometers, time-of-flight ion mobility spectrometers, as well as field asymmetric ion mobility spectrometers (FAIMS).
Mass spectrometers identify molecular components according to their characteristic “weight” or mass-to-charge ratio. Typically, a mass spectrometer-based analytical system includes the following components: a device for introducing the sample to be analyzed, such as a liquid or gas chromatograph, direct insertion probe, syringe pump, or autosampler; an ionization source for producing ions from the analyte (as referred to herein, an analyte is the sample itself or one or more components of the sample); an analyzer for separating the ions according to their mass-to-charge ratio; a detector for measuring the abundance of the ions; and a data processing system that produces a mass spectrum of the analyte.
Mass spectrometers are very sensitive, highly selective, and provide a fast response time. Mass spectrometers, however, are large, expensive, and require significant amounts of power to operate. They also often require several different types of pumps to maintain a vacuum-pressure in the analyzer region of about 10−6 Torr in order to isolate the ions from neutral molecules and to permit detection of the selected ions.
Another, less complex spectrometric technique is time-of-flight (TOF) ion mobility spectrometry, currently implemented in most portable chemical weapons and explosives detectors. TOF spectrometry is not based solely on mass, but is also based on charge and cross-section of the molecule. While conventional TOF devices are relatively inexpensive, they suffer from several limitations. First, molecular species identification via TOF spectrometry is not as conclusive and accurate as via mass spectrometry. Time-of-flight ion mobility spectrometers typically have unacceptable resolution and sensitivity limitations. The sample volume through the detector of a TOF spectrometer is small, so in order to increase spectrometer sensitivity, either expensive electronics are required to provide extremely high sensitivity, or a concentrator is required, adding to system complexity and cost. In addition, a gate and gating electronics are usually needed to control the injection of ions into the drift tube. Miniaturization, or micromachining, of TOF spectrometers worsens sensitivity. For example, problems occur when the drift tube length of a TOF spectrometer is less than about 2 inches. In time-of-flight ion mobility, the resolution is typically proportional to the length of the drift tube. The longer the tube, the better the resolution, provided that the drift tube is also wide enough to prevent ions from being lost to the side walls due to diffusion. Thus, fundamentally, miniaturization of TOF ion mobility systems leads to a degradation in system performance.
Yet another technique, field asymmetric ion mobility (FAIM) spectrometry, allows a selected ion to pass through a filter while blocking the passage of undesirable ions. Conventional FAIM spectrometers are large and expensive; for example, current devices are nearly a cubic foot in size and cost over $25,000. These systems are not suitable for use in applications requiring small detectors. They are also relatively slow, taking as much as one minute to produce a complete spectrum of the sample gas, they are difficult to manufacture, and they are poorly suited for mass production. Moreover, the pumps that are required to draw a sample medium into the spectrometer and to provide a carrier gas can be rather large and consume large amounts of power.
Recently, microDMx™ sensor chip technology, an improvement over conventional FAIM spectrometry, has been developed by The Charles Stark Draper Laboratory (Cambridge, Mass.) (“Draper Laboratory”) and is presently available from Sionex Corporation (Waltham, Mass.) (“Sionex”). This sensor chip technology, as described in, for example, U.S. Pat. Nos. 6,495,823 and 6,512,224, which are both incorporated herein by reference, demonstrates that extremely small, accurate, and fast FAIM filter and detection systems can be implemented using MEMS and microfabrication technology to define a flow path between a sample inlet and an outlet using a pair of spaced substrates and disposing an ion filter within the flow path. The filter includes a pair of spaced electrodes, with one electrode associated with each substrate, and a controller for selectively applying a bias voltage and an asymmetric periodic voltage across the electrodes to control the path of ions through the filter. In its various aspects, this technology separates and detects ionized compounds based on their differential mobilities through the sensor chip described above. Ionized compounds have mobilities, which are a function of their charge, mass, and cross-sectional area. By applying an RF and DC field to the sensor chip it can act as a filter selecting a chosen ion or collection of ions. The applied DC and RF fields can be used as parameters to identify the ions together with additional information, such as field dependence. This differential mobility spectrometer device (“DMS”) is small, inexpensive, highly sensitive to the parts-per-trillion range and is capable of detecting a variety of chemicals and biological materials.
One obstacle to utilizing this technology to its full potential, however, is the methodologies currently used to ionize and introduce the samples into the DMS for analysis. Current methods of introducing samples into the DMS include the following: headspace sampling, pyrolysis, gas sampling, and conventional gas spectrometry (i.e. volatilizing and separating samples using a Gas Chromatography (GC) column). Each of these current methods have drawbacks.
In headspace sampling, gaseous volatiles in the headspace above liquid samples are directed through a Gas Chromatography (GC) column to separate components in the sample, which are then introduced into the DMS. Alternatively, the gas volatiles may be introduced directly into the DMS for analysis. This method is limited to analysis of volatiles in the headspace above liquid samples. Semi-volatile and non-volatile components, however, are difficult to examine with this sample introduction technique because of their low vapor pressure and resulting low concentration in the headspace above the liquid sample.
Pyrolysis involves breaking-apart chemical bonds using thermal energy. The resulting molecular fragments are often ion species. Both solid and liquid samples can be pyrolyzed. The resulting gas is directed through a GC column, then introduced into the DMS. Alternatively, the pyrolyzed material may be introduced directly into the DMS for analysis. Pyrolysis, however, is destructive of large molecular weight samples, and, as such, this technique often results in excessive fragmentation of the molecules. It may be impossible to detect certain higher molecular weight compounds using this technique.
In gas sampling, gaseous samples are introduced directly into the DMS, or are passed through a GC column, then introduced in to the DMS. This method is limited to examination of gaseous samples.
For certain volatile and semi-volatile liquid organic compounds, samples can be volatilized and separated using the GC column, and then transported into the DMS. Again, this is not possible for analysis of non-volatile substances, or for certain semi-volatile substances.
Current methods of ionizing samples for analysis in the DMS include the use of the following: UV-photoionization lamp, radioactive 63Ni and 241Am sources, and plasma corona discharge devices.
A UV-photoionization lamp may only be used to ionize substances with ionization potentials up to 11.7 eV, making such methods suitable for processing certain volatile and semi-volatile compounds, but not non-volatile liquids. Also, the surface of the bulb often becomes coated with residues from sample introduction, reducing ionization efficiency.
Radioactive 63Ni and 241Am sources provide ionization energy of up to 67 keV and 59.5 keV, respectively. Radioactive sources must be registered with government and institutional safety offices. Special handling licenses are required. These requirements restrict the widespread use of these ionization sources in non-R&D devices, keeping them from being truly mobile or field-deployable.
Thus, limitations of conventional methods of sample preparation for spectral analysis using a differential mobility spectrometer (DMS) impede exploitation of this potentially versatile device, particularly for analysis of bio-organic molecules, microorganisms, and other biological compounds, as well as high molecular weight non-biological compounds such as polymers and hydrocarbons. Specifically, there is a need for systems and methods for ionizing and converting non-volatile and/or semi-volatile biological and other macromolecular analytes into the gas phase for analysis in a DMS, i.e. a FAIMS, preferably without fragmentation of the molecules. There is also a need for portable analysis systems with micromachined components, as well as systems that do not require operation under high vacuum.